We propose to continue studies on aspects of innate defense mechanisms against Candida albicans. These studies should allow us to make definitive conclusions regarding how congenitally thymic deficient (nude) mice resist C. albicans better than normal mice. We have determined that nude mice possess a peritoneal cell that is candidacidal whereas similar cells from normal mice are candidastatic. By fractioning peritoneal cells using density gradients, specific antisera, and the differences in adherent characteristics we will isolate and identify the candidacidal cell. Isolated cells will then be adoptively transferred to normal mice to show that this cell type plays a role in protection against candidiasis. Attempts will also be made to activate similar cells to become candidacidal in normal mice. These latter experiments will help to explain not only the mechanism of cell activation occurring in nudes but also may provide basic information for future immunotherapeutic measures against human opportunistic fungal diseases. Previously we demonstrated that C. albicans produces a substance which attracts neutrophils in vitro. We are developing an in vivo model to assess whether the factor is produced and is active in vivo. Also, antibodies to the chemotactic factor will be developed and applied experimentally to determine the role of chemotactic factor in pathogenesis of candidiasis. Candidiasis is a major nosocomial disease and we believe our studies will lead to an understanding of mechanisms which render an individual resistant to the disease.